Ebolaviruses (family Filoviridae) cause severe hemorrhagic fevers in humans and nonhuman primates, with mortality rates as high as 90% (Sanchez et al., 2007). Ebolaviruses and the closely related Marburgviruses belong to the Filoviridae family (Feldman et al., 2004). Currently, there are no approved vaccines or antivirals for use against filoviruses. Antivirals are not only desirable for local populations in epidemic areas and for health care workers during an outbreak, but also for researchers studying these viruses. Short interfering RNA molecules (Geisbert et al., 2006), and S-adenosylhomocysteine hydrolase inhibitors (Bray et al., 2000; Huggins et al., 1999) have been shown to inhibit Ebola viral growth in vitro and/or in vivo. However, the most effective approach to filovirus control will likely come from a combination of pharmacologic agents with different mechanisms of action (Bray & Paragas, 2002).
High throughput molecular screening (HTS) is an automated, simultaneous testing of thousands of distinct chemical compounds in models of biological mechanisms or disease. Since authentic Ebolaviruses are biosafety level 4 (BSL-4) agents, HTS with the viruses is not feasible. The lack of sufficient BSL-4 space, trained personnel, and the rigors of working in BSL-4 laboratories have severely hampered basic research with Ebolaviruses as well as the development of vaccines. These limitations have prompted examination of various steps in the Ebolavirus viral life cycle in the absence of infectious virus: (i) replication and transcription were studied by use of reporter gene assays that are based on the expression of necessary viral components from plasmids (Boehmann et al., 2005; Groseth et al., 2005; Muhlberger et al., 1999; Modrof et al., 2003; Modrof et al., 2002); (ii) entry and fusion processes were assessed with pseudotyping assays that rely on the use of recombinant vesicular stomatitis or retroviruses (Yonezawa et al., 2005; Wool-Lewis et al., 1998; Takada et al., 1997; Marzi et al., 2006); and (iii) budding was examined using virus-like particles that are generated from viral proteins provided by protein expression plasmids (Jasenosky et al., 2001; Licata et al., 2004; Noda et al., 2002; McCarthy et al., 2006; Johnson et al., 2006). However, several recent findings suggest that data obtained with these artificial systems may not always be reproducible with live, authentic Ebolavirus (Neumann et al., 2005).